Basic Tilted Helix Bundle - a new protein fold in human FKBP25/FKBP3 and HectD1

Biochem Biophys Res Commun. 2014 Apr 25;447(1):26-31. doi: 10.1016/j.bbrc.2014.03.068. Epub 2014 Mar 22.

Abstract

In this paper, we describe the structure of a N-terminal domain motif in nuclear-localized FKBP251-73, a member of the FKBP family, together with the structure of a sequence-related subdomain of the E3 ubiquitin ligase HectD1 that we show belongs to the same fold. This motif adopts a compact 5-helix bundle which we name the Basic Tilted Helix Bundle (BTHB) domain. A positively charged surface patch, structurally centered around the tilted helix H4, is present in both FKBP25 and HectD1 and is conserved in both proteins, suggesting a conserved functional role. We provide detailed comparative analysis of the structures of the two proteins and their sequence similarities, and analysis of the interaction of the proposed FKBP25 binding protein YY1. We suggest that the basic motif in BTHB is involved in the observed DNA binding of FKBP25, and that the function of this domain can be affected by regulatory YY1 binding and/or interactions with adjacent domains.

Keywords: FKBP25; FKBP3; HectD1; Immunophillins; NMR structure; Structural genomics; YY1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid
  • Tacrolimus Binding Proteins / chemistry*
  • Tacrolimus Binding Proteins / metabolism
  • Ubiquitin-Protein Ligases / chemistry*
  • YY1 Transcription Factor / metabolism

Substances

  • YY1 Transcription Factor
  • YY1 protein, human
  • FKBP3 protein, human
  • HectD1 protein, human
  • Ubiquitin-Protein Ligases
  • Tacrolimus Binding Proteins